There are extensive biological, medical and industrial uses for small polymeric particles having uniform size and even more extensive uses for magnetic polymeric microspheres. Small polymeric microspheres, especially those containing covalent binding functional groups, are finding increasing uses in separation processes such as affinity chromatography, in labelling and sorting of biological cells, in diagnostic testing and in clinical treatment. Metal and metal oxide containing microspheres, particularly those containing magnetically susceptible materials, find use in catalysis, and electron microscopy. Uniformly-sized particles can be utilized to calibrate instruments or filters and the like.
Magnetic particles also find use in biology as substrates or carriers for enzymes or proteins and in cell biology as substrates derivatized with ligands capable of labelling specific cells. The labelled cells can then be separated from a mixture containing both labelled and unlabelled cells or from mixtures of labelled cells with other proteinaceous material. Magnetic microspheres can also be utilized to deliver a pharmaceutical to a specified location or organ in an animal or person.
Microspheres containing magnetic oxides and/or electron dense metals such as iron can also be useful in cell identification by electron microscopy. Rembaum, et al (Science, 208: 364, 368, [1980]) disclose identification of malignant cells in mixture with normal cells by this technique. U.S. Pat. No. 4,169,804 discloses use of magnetic-ligand particles for measurement of hormones and vitamins. Magnetic microspheres labelled with specific antibodies have also been utilized to specifically bind to malignant cells in the treatment of leukemia.
Magnetic polymeric microspheres have been used, for example, to remove cancerous cells from bone marrow as a treatment for neuroblastoma. The antibody-containing microspheres were mixed with both normal and cancerous bone marrow cells. The antibodies attached the microspheres only to the cancerous cells. The microsphere-cell conjugates were then removed from the solution by being attracted to a strong magnet placed adjacent the wall of the container. The cleaned marrow cells were then reimplanted in the patient. To date, 55 patients, many of them children, have been treated by this technique with promising results (Treleaves et al, Lancet, pp. 70-73, Jan. 14, 1984). Molday, et al., (Nature, 268: 437-438 [1974]) and U.S. Pat. Nos. 4,157,323; 4,177,253; and 4,267,235 also disclose use of magnetic microspheres in the labelling and separation of specific animal cells.